PB1830: THE PROGNOSTIC AND PATHOGENETIC SIGNIFICANCE OF СOMPONENTS OF NEOPLASTIC INFLAMMATION AND CYTOKINES IN THE ADULT WITH ACUTE LEUKEMIA
Authors: Vira Barilka, Volodymyr Matlan, Olha Shalay, Sofiya Prymak, Vasyl Novak
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Components of neoplastic inflammation, such as tumor-associated lymphocytes, cytokines, tumor necrosis factor (TNF) and transforming growth factor beta 1 (TGFβ1), the phagocytic activity of peripheral blood mononuclear cells (PBMC) against leukemic cells, the number of neutrophils, are the first line of defense against leukemia. On the other hand, we hypothesize that components of neoplastic inflammation may have a pathogenetic influence on the progression and survival of acute leukemia (AL) patients (pts). However, the prognostic value of these components has not been definitively established. Aims: To investigate the prognostic and pathogenetic significance of components of tumor inflammation, cytokines in the peripheral blood of adult with AL. Methods: For this purpose, the peripheral blood of 20 adult AL were studied. Bone marrow punctate, hemogram, and clinical status were used to establish AL (FAB, 2016). The concentration of TNF, TGFβ1 was determined in the plasma and 24-hour supernatants from the primary culture of PBMC of AL pts. The control group consisted of 15 healthy people. The phagocytosis of PBMC (mix of lymphocytes with blasts) was determined in co-culture with K562 cells in vitro (ratio of 1:20) by biological methods. Statistical processing of the results was carried out in Excel. Results: Pts were divided into two groups (Gr.) based on response to treatment. There were 10 primary untreated pts with acute myeloblastic leukemia (AML) and 5 pts with acute lymphoblastic leukemia (ALL). They were included in Gr.A. Average survival was 115 days. The concentration of TNF in plasma and supernatants of PBMC significantly exceeded the values in healthy individuals; p < 0.01, in both cases. The concentration of TGFβ1 was not significantly different from the control. Phagocytosis of PBMC in Gr.A was higher than in controls; p˂0.05. A direct correlation was established between phagocytosis and the level of TNF in the supernatants of PBMC (r= 0.52), as well as an indirect correlation was between phagocytosis and leukocytes (r= – 0.53) and lymphocytes (r= – 0.43). In Gr.B. there were 5 ALL pts with relapse. Average survival was 32 days. The number of leukocytes, lymphocytes, blasts was significantly lower than in Gr.A. However, the phagocytic activity of PBMC was significantly higher than in group A (p <0.001) and control (p <0.001) and positively correlated with the number of blasts (r=0.72) and with the concentration of TGFβ1 in the supernatants of PBMC pts (r=0.8). The concentration of TGFβ1 in plasma Gr.B statistically exceeded the indicators in Gr. A and in the control; p < 0.05, in both cases. Summary/Conclusion: Thus, the obtained results indicate that the components of neoplastic inflammation are related to the pathogenesis of AL and can be used as additional prognostic factors. In particular, they are important for interpreting the explanation of disease recurrence, treatment sensitivity and survival. On the other hand, they may testify to the tumor-associated role of inflammation in the regulation of phagocytic properties of PBMC, which may be one of the mechanisms of AL progression, in particular, as a result of the destruction of normal hematopoietic progenitor cells. On the other hand, we do not exclude that lymphocytes, together with blasts, may be promising targets to achieve the regulation of autophagy of blasts themselves under the influence of secreted cytokines, a phenomenon called spontaneous remission. Keywords: Prognostic factor, Cytokine, Acute leukemia, Inflammation